Economic evaluation of vaccination against COVID‐19: A systematic review

Abstract Background and Aims Coronavirus has burdened considerable expenditures on the different health systems. Vaccination programs, the critical solution against pandemic diseases, are known as safe and effective interventions to prevent and control epidemics. We aimed to perform a systematic review to provide economic evidence of the value of different types of vaccines available to combat the Covid‐19 to all health policymakers worldwide. Methods Electronic searches conducted on Medline/PubMed, Cochrane Library, Web of Science, Scopus, Embase, and other economic evaluation databases. Related and published articles searched up to March 2022 by using keywords such as “Vaccination,” “Covid‐19,” “Cost‐benefit,” “Cost‐utility,” “Cost‐effectiveness,” “Economic Assessment,” and “Economic evaluation.” Followed by choosing the most suitable articles according to inclusion and exclusion criteria, data captured and the results extracted. The quality assessment of the articles performed by the checklist of CHEERS 2022. Finally, 13 articles included in the review. Results All messenger RNA vaccines were dominant with approximately 70% coverage against no vaccination in the primary vaccination program except in one study that looked at booster effects. From a payer's perspective, a dollar invested in a vaccine would be less profitable than from a societal perspective. Therefore, primary mass vaccination can be considered a cost‐effective intervention in primary vaccination to save more lives and produce more positive externalities. However, the cost‐benefit ratio for all vaccines increases when statistical lifetime value and global economic and educational disadvantages are considered. Conclusion The COVID‐19 primary vaccination programs in regional outbreaks, from a long‐term perspective, will demonstrate substantial cost‐effectiveness. It is suggested that due to the positive externalities of vaccination, primary mass vaccination, with the help of COVAX‐19TM, could be considered a reliable way to combat viral epidemics compared to the loss of individual lives and economic and educational disturbances around the world.


| INTRODUCTION
[3] Subsequently, this situation has made global economic contractions, difficulties and recessions, economic downturns, and crises mainly due to medical expenses and productivity loss worldwide. 3,4New research on the Covid-19 vaccine showed that people attitudes towards the Covid-19 vaccination, specially the role of potential policy options, characteristics of the vaccine, and disinformation plus misinformation played an important role in people's acceptance of vaccination. 5In two recent studies the researcher noted that vaccines with higher efficacy were associated with a greater chance of vaccination acceptance, while emergency use authorization by the Food and Drug Administration 6,7 or vaccines that required more time for political approval were associated with greater uncertainty. 8In another very recent study, the researchers are going to show that risk perception and trust in health institutions are the most relevant predictors of intention to be vaccinated. 9[12][13] Despite severe public health policies that have been implemented in most of the involved countries to prevent COVID-19 transmission, the pandemic cessation has not entirely succeeded.
Therefore, to deal with this problem, it was necessary to identify effective pharmacological interventions and found a more reliable strategy for prevention such as vaccination. 14Despite the goals of the Immunization Agenda 2030 (IA2030) campaign to further strengthen global immunization and reduce global disparities, the global COVID-19 pandemic has led to further disruption of routine immunization and campaign activities.It has been estimated that even if the IA2030 targets were met, the epidemic would have resulted in at least 50% fewer fully vaccinated persons and 5.22% more deaths worldwide. 15 this regard, scientists and researchers in different countries attempted to discover an effective vaccine to reduce viral transmissibility and finally control disease consequences. 16,17Considering the insufficiency of the available preventive measures, it seems prophylactic vaccination is a cost-effective and promising remedy provoking immunity by stimulating neutralizing antibody production and memory T lymphocytes to fight the pathogen and diminish disease transmission. 18 the other hand, although vaccination may be a critical achievement in this challenging situation to address this health problem, there are concerns regarding the costs of preparation.
When dealing with the costs of public vaccination, which is different according to the type of vaccine and estimated to be approximately $50 billion to save the world, usually there is no limitation for highincome countries, whereas the majority of countries are not able to access sufficient amount especially low and middle-income countries. 11,19,20So, a big dilemma is providing sufficient financial sources to implement vaccination programs for a large number of populations in a short time.Nevertheless, it is supposed that this huge cost prioritizes and prevents more devastating economic impacts of COVID-19. 21,22cording to the World Health Organization (WHO) COVID-19 vaccine tracker and landscape, by the start of April 2022, 153 vaccines are in clinical development and 196 in preclinical development. 23Moreover, as of April 4, 2022, more than 11 billion vaccine doses have been administered worldwide to encounter COVID-19. 24, the availability of different vaccination choices justifies a cost evaluation for better investment which is worthy of healthcare systems and policymakers.Furthermore, though vaccination is inevitable to creating herd immunity against coronavirus and its variants of concerns, the providing and deciding about financial aspects of vaccination programs (the type of vaccine and the priorities) depending on each country are also critical. 25nce, a cost-effectiveness analysis (CEA) is needed to respond to related questions, including; is vaccination cost-effective in coping with the pandemic?What are their economic benefits?Moreover, it should determine the cost of ending the pandemic through vaccine investments.Therefore, this study systematically reviews the economic evaluation studies regarding the economic evaluation of the Covid-19 Vaccine.It hopes to provide useful economic information for health systems and help categorize their priorities regarding the type of vaccine for their country.

| Search strategy
In this study, required data was determined using Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) criteria. 26In this systematic review, Scopus, Medline/PubMed, Web of Science Core Collection, Cochrane Library, Google Scholar, Embase (Excerpta Medica Database) is a biomedical and pharmacological database produced by Elsevier databases were searched to identify articles related to the economic evaluation of Covid-19 vaccine.All published studies up to March 2022 were included.To identify additional articles, the references mentioned in the main published articles were also searched.

| Study selection
Independently, titles and abstracts identified in the articles were screened by two authors for obtaining the cost-effectiveness reports of the Covid-19 vaccine.Then, the full text of the selected studies was reviewed according to the inclusion and exclusion standards.
Articles were screened by two authors and the results of each were compared.The unresolved discrepancies among reviewers were discussed and finalized by the third one.

| Inclusion and exclusion criteria
The inclusion criteria based on the PICO protocol were consisted of:

| Quality assessment
In terms of methodology, the quality assessment of final articles was performed latest version of the Consolidated Health Economic Evaluation Reporting Standards CHEERS checklist (2022).This checklist consists of 28 questions to evaluate economic evaluation studies.Two independent reviewers sorted and graded one by one the selected articles in this review. 27,28A decision on any disagreement was assigned and affirmed by a third arbitrator.Items that fully met the checklist in the selected studies were scored "1" and addressed as "Y."Partially concordant cases received a score of "0.5" and were designated as "P," and no concordant cases received a "zero" score and were designated as "N."The high quality studies constituted >85% followed by very good quality <70%-85%, good <55%-70%, and low quality studies <55%. 29,30| RESULTS

| Included studies
In the initial assessment of this study 1618 associated citations were retrieved that 451 out of all were obtained from PubMed.Afterward, 725 duplicate citations were removed, and 893 studies based on their abstracts and titles remained.Next, 689 studies were excluded according to the inclusion standards and finally 204 abstracts were fixed for the full-text screen.From all, 191publications were ignored considering the inclusion criteria and the CHEERS checklist was used to evaluate studies with inadequate results or methodology.
Eventually, the presented systematic review was carried out on 13 selected studies.The review selection strategy based on the PRISMA guidelines was presented in Figure 1.

| General characteristics of the studies
A total of 13 studies were reviewed according to included and excluded criteria.The studies were published between 2020 and the end of 2021.Studies have used various economic analyses to evaluate the Covid-19 vaccine.One study used both cost-utility and CBA, 31 one CBA study, 32 and one CUA study. 33One study also used both cost-effectiveness and CBA. 34The other rest studies were of the CEA type.The studies have been performed in different countries.One study in Taiwan, 31 one study from Brazil, 33 one from Poland, 35 one from Hong Kong, 36 one from Turkey, 37 and one study in six Western Pacific and southeast Asian countries, 38 one study in Catalonia, 32 three studies in the United States, 34,39,40 one from Pakistan, 41 one from Denmark 42 and One study in Iran. 43Table 1 exhibits the characteristics of the studied articles.
Their perspectives has been defined as follows: two studies were from both healthcare and partial societal perspectives, 34,41 three studies from a healthcare sector perspective, 36,39,42 one study from the healthcare system perspective, 40 three studies from a healthcare payer perspective, and societal, 31,32,37 a study from the perspective of the public health system, 33 a study from the perspective of public healthcare payer, 35 and a study from a societal perspective. 38n all studies except one study, 32 the designed model of the studies was the Dynamic Transmission Model, Markov model, and Decision Tree.Two studies used a dynamic micro simulation model, 37,42 two studies used a Decision Tree 34,38 and seven studies used the Markov simulation model 31,33,35,36,[39][40][41] to extract longterm data.
A time horizon is determined to review and follow up the interventions as well as their outcomes and costs in economic evaluation studies.In our selected studies, different time horizons are considered.There was a study with a time horizon of 180 days, 31 another with 10 years, 41 and also 6 months. 42Also, two studies did not mention the time horizon. 32,40Other studies have had a 1-year time horizon.
In different entered studies, discount rates have been dedicatedly assigned to alleviate costs and outcomes.For instance, 3.5% discount rate was applied in one study. 35In another study, a 3% discount rate was used to reduce costs and effectiveness. 37,38,41Two studies have also indicated that the discount rate has not been used due to the time horizon type. 32,34In the study of Debrabant et al., 42 a discount rate of 2%-4% was used to discount the effectiveness.Different health outcomes have been performed in the studies.
In eight studies, only QALY [31][32][33]35,36,[38][39][40] and in one study, only LY (life-years) was used as a health outcome 34 ; and one study used both QALY and LY, 42 in two studies, DALYs was used to measure the health outcome. 37,41,43 Insome studies, the predominant intervention was vaccination versus non-vaccination, but the type of vaccine was not mentioned.32,[36][37][38][39][40][41][42] In one of the studies, universal vaccination was compared with the Risk stratified vaccination approaches.34 In the study of Wang et al., 31 the intervention evaluated the vaccines of Pfizer, Moderna, and Oxford in comparison with nonvaccination.In another study, the intervention evaluated Oxford, CoronaVac, and Janssen vaccines in comparison with nonvaccination, 33 and in another study, Comirnaty vaccine (BNT162b2) in comparison with non-vaccination. 35In 5 of the 12 studies included, the type of vaccine was identified for analysis. On study looked at three vaccines, Pfizer, Moderna, and AstraZeneca, 31 and another looked at three vaccines, Oxford, CoronaVac, and Janssen.33 Other studies have examined the Comirnaty vaccine (BNT162b2), 35 Sinovac, BioNTech, 36,39 and HB02, CoronaVac, 38 respectively.
In Table 2, the qualitative evaluation results of 13 studies are presented and it shows that all 13 studies passed the checklist and no study was excluded.

F I G U R E 1
The procedure of systematic literature search strategy, it was in accordance with the preferred reporting items for systematic review.
T A B L E 1 Characteristics of evaluated studies.With 330 million population in the United States, without calculating the vaccination costs, the direct medical burden costs of the Covid-19 epidemic on the healthcare sector have been estimated at about $34 billion in a year.The cost of the vaccination program has been estimated at $13,042 billion.The disease also caused 6.3 million days of hospitalization and more than 283,000 deaths, and the cost of reducing productivity lost due to the disease was estimated at $32 billion. 39In one study, the cost of healthcare was reduced from 2.4 million DKK (The Danish krone) to 1.5 million DKK when people were vaccinated.These reduction costs included hospital costs, testing costs, and follow-up costs in Denmark (Table 3). 42

| Uncertainty analysis
Except for one study, 32 type of sensitivity analysis has been introduced in the other studies.A variety of one-way, multiple, and probabilistic sensitivity analyzes have been performed to identify parameters that affect the stability of ICER results.Three studies of one-way sensitivity analysis and probabilistic sensitivity analysis (PSA), 36,38,39 one study of PSA, 33 six studies of single-way sensitivity analysis 16,35,37,[40][41][42] and one study used all three types of sensitivity analysis one way, two-way, PSA sensitivity analyzes. 34cording to the results of the sensitivity analysis, some parameters are responsible for reducing the incremental cost-utility T A B L E 3 Summary results of included economic evaluation studies.for all groups of ages.Based on the payment threshold, all kinds of vaccines for patients over 60 years have been observed costeffectiveness; whereas CoronaVac and Janssen showed that it is not a true theory in subjects less than 59 years old. 33Moreover, the ICER was stricter to vaccine effectiveness, price, and SARS-CoV-2 infection rate in the general public and younger individuals. 35In another study in the Hong Kong, ICER decreased with increasing infection rate and gradually approached to the willingness-to-pay threshold of this country.Similar to the results of the Polish study, 35 other authoritative variables on ICER rates, were vaccine price, vaccination rate, and hospitalization cost. 36sed on the results of sensitivity analysis of one study, one of the most influential parameters on the ICER rate was the number of susceptible people in the community.Also, a 2% increase or decrease in the cost of vaccination affected 10% on the ICER. 37In one study, the amount of net monetary benefit (NMB) also elevated along with the COVID-19 incidence and vaccination implementation. 39 a study conducted in the United States, the results of a oneway sensitivity analysis showed the strength of the costeffectiveness results by changing the parameters.Some parameters, such as vaccine cost, vaccination rate, and effectiveness of vaccine had the most significant influence on the results.The results of PSA also showed that at the threshold of willingness to pay $100,000/ QALY, the vaccination option was cost-effective. 40 another study in the United States, ICER results were highly sensitive to the parameter alterations in attack rate, vaccine price, and costs of hospitalizations; and the least effect on outcomes were related to the patient's disutility due to morbidity.According to the study, the target population-specific vaccine should cost more than $150 per dose to exceed the incremental cost of more than $50,000 per QALY. 40As same as the other studies vaccine price, implementation costs, and plus the discount rate used to estimate LY & QALY gained affected the ICER results in the Danish study model. 42Global vaccination prevents 97,071 deaths and saves cost more than $17 billion.According to the results of the PSA, global vaccination with 99.58% would be the most cost-effective strategy. 343). 35e vaccination program, which has reached about 72% of Hong Kong's population with two doses of the vaccine, cost the Hong Kong Dollar (HKD) 22,339,700 per QALY obtained before the Omicron wave and was not cost-effective at the threshold of willingness to pay in this country.However, the cost-effectiveness of the Covid-19 vaccination program was highly sensitive to the infection rate.In the Omicron outbreak in this country, HKD 310,094 was determined for the vaccination program ICER, and the vaccination program in the Omicron outbreak has been cost-effective. 36From a socially perspective Shaker study in Canada, despite some universal challenges to side effects of the vaccine like the anaphylaxis, global vaccination has been considered a cost-effective approach unless the vaccine anaphylaxis risk was greater than 0.76%. 34tate Dollar (USD) $50,000 as the wiliness-to-pay, primary mass vaccination probably was around 70% cost-effective. 31It can be argued that different rates of cost-effectiveness of vaccination programs between countries are because the background of the epidemic has varied between different regions, as well as how countries have dealt with the Covid-19 outbreak and the extent of their control measures.The western countries, for example, generally had fewer strict control measures and the disease had been more prevalent.Therefore, as the epidemic intensifies and the rate of infection increases, the vaccine becomes more targeted and leads to fewer deaths, and less money lost. 38 recent years, due to the unexpected prevalence of Covid-19

| Cost-effectiveness outcomes
and the unpreparedness of human societies to deal with its adverse consequences such as death, tremendous expenditures have been spent on finding the most cost-effective treatments, so most economic evaluations instead of preventable methods such as vaccinations have focused on the treatment of Covid-19.And some treatments such as Remdesivir and Dexamethasone have shown cost savings and death prevented. 44As two studies have demonstrated that the administration of primary mass vaccines of Covid-19 compared to its treatment methods in countries with different economic levels have remained a complementary cost-saving and cost-effective. 32,39And assuming an epidemiological model with native data on demographics, social communication arrangements, costs of the healthcare system, gross domestic product (GDP), human productivity, and their salaries that has been mathematically modified into four sections including Susceptible, Infectious, Recovered, and Death; it could be applicable to conceptually representative for other countries as well. 32However to meet the global demand for vaccines, and conquer distributive challenges in the supply chain, the current vaccine production should be increased logistically; on another side vaccine prices are variable from country to country, and the beneficiary of vaccination may not be the same across the different populations.Therefore in this situation, the use of both vaccines and treatments is recommended by the researchers of the western countries. 41e results of some studies in the low-middle-, and high-income countries in the western Pacific and Southeast Asia have shown that vaccination is not only cost-effective but also has significant NMBs.
This means that with the growth of prevalence of Covid-19 and the population coverage of vaccination, the NMB will increase.And regarding the high population density and large population of these regions, protecting the population against COVID-19 would be considered an important policy intervention.For example, the incremental cost-effectiveness ratio (ICER) for a primary vaccination with Covid-19 vaccines was estimated at 6.2-121.2USD to avert one DALY and 566.8-10,957.7 USD per death in Iran. 40,43cording to one of the European studies, in terms of health policy, designating the vaccination movement has been known as a very effective strategy in restraining the disease; accounting, the whole of Catalonia and Spain, for savings of 227 and 1447 million euros from the health system perspective.By the direct effect of vaccination, the study estimates the avoided cases and recommends that a third dose of the vaccine not only preserves the cost-benefit ratio but also would extend the duration of its positive effects; therefore, the results would indicate a lower threshold in the number of hospitalizations, ICU admissions, PCR, and RAT tests, and prevention mortality. 41 prospect the relative value of vaccines, and provide evidencebased information to the American healthcare sector, policymakers, and generalize the findings to the other health systems around the world, some researchers based on the US economy using an economic model, despite a negative ICER at the threshold of $100,000/QALY, have predicted that existing vaccines can have a significant increase in effectiveness at a lower direct cost than doing nothing.And in their findings, the cost-effectiveness acceptability curve showed cost-effectiveness at threshold.However, the attack ratio for the year after vaccination is the disadvantage of using value.
Prediction of mortality among common pattern is limited to a few months later, and changes in health policies or personal behavior may modify the long-term certainty of the disease. 40,41timates of some studies have shown that the value of vaccination in low-risk groups (less than 50 years old) is significantly inferior to that value in older ages.Analyzing in this way makes some misunderstanding; for example, the group under 50, despite being at low risk of severe disease from Covid-19, has shown the main role in spreading the disease in the communities, and their vaccination value has been underestimated as a preventable intervention for all the population; and in the other hand, many of the other societal costs such as their productivity associated with the pandemic has been refused to be noticed. 42 the other hand, there are different population stratifications in different studies estimating the vaccines effectiveness. 33Some of their evidence in Poland showed that in elderly, high-risk, and vulnerable populations, vaccination was the first choice in controlling morbidity and mortality, especially in the early stages of vaccine administration. 35Although targeting older people in high-income countries will initially be much more cost-effective, some studies in low-income countries have shown that these benefits are not particularly age-dependent.In some low-income countries such as Pakistan, individual vaccination would be cost-effective if the vaccine production and delivery costs would be at $10 a dose or had an effectuality up to 30%; and despite the results of Taiwan's study, 31 primary mass vaccination program in several years may evacuate insufficient resources from the other part of the Pakistan's health services, and could not be considered a cost-effective intervention.
Assuming a 1-year vaccination in such countries, the cost would be a further $2 million in comparison with non-vaccination, avoiding 70,000 DALYs, which would gain a $28 ICER per DALY.And assuming a 5-10-year vaccination, it would have higher incremental costs ($228-454 per DALY, respectively) and more avoided DALY. 41 we mentioned above, vaccination in the age group under and above 50-60 had different ICERs in different countries, and when we included the productivity losses of the younger group and reduced the price of the vaccine, the efficiency and cost of the vaccine increased.In addition, the results showed that as the target group expanded, from the elderly to younger populations, an increase in cost per life year emerged.Based on the findings of Debrabant 42 and their colleagues in Denmark, although we account for the ICER by the vaccine prices and hospitalization costs, this increasing cost may come from the marginal products of vaccination with its increasing costs; which pursues the low mortality rate of the Covid-19 among those under 60 years free from hospitalization and vaccine costs. 42en comparing the risk stratification with global vaccine coverage, the researchers found that the risk of anaphylactic reaction was  34 To check the robustness of the cost-utility or CEA of the Covid-19 vaccine with variable values of parameters, including the reproduction number, and Monte Carlo simulations, the sensitivity analyses have been applied in some selected studies. 16,37,39,41,42And they showed that reproduction numbers ranged from 1.7 to 2.8 above one (lower bound to upper bound) in different rounds of the models in which the vaccination intervention was performed, and as a result, the healthcare costs were lower with the vaccination program than without vaccination.However, one of the studies 35  induced immune responses in individuals with mild previous infection are generally higher, 47 as previously infected individuals who were given one dose of a COVID-19 vaccine have higher responses than full schedule vaccination of people who had not been previously infected. 48,49Accordingly, it seems that for previously infected individuals a one-dose plan might be adequate to reach the dual pursuit of covering populations and preserving stockpiles.Moreover, this statistic could be considered as the geographic distribution of the virus and also the primary measures that every region had taken place at the right time.On people acceptance, although we have seen varying degrees of vaccine hesitancy across countries, the impact appears to have been relatively small as acceptance of COVID-19 vaccines is likely to change over time as stronger evidence and monetary incentives emerge.And, last but not least, healthcare system requirements for vaccination include executing adequate systems to document vaccine administration and activating effective reminder systems, providing immunization services without disparities by integrating healthcare services, logistics capacity, and workforce distribution.
Based on the retrograde picture of COVID-19 vaccination policies, and conditional on the different countries' sociodemographic index, healthcare access and quality Index, GDP per capita adjusted for purchasing power parity (PPP), and as well as PPPadjusted government health spending per capita, it is assessed that the disparity in vaccination coverage around the world implies that the susceptibility of unvaccinated populations in some countries may impede or boomerang pandemic management, especially in encountering new variants of COVID-19 such as Omicron and other future emerging variants.Hence, more countries and organizations must be engaged in the global reaction to pandemics, take responsibility, enhance their national and regional accountability, and deliver leadership to overcome the complicated onrush challenges politically, technically, and financially.

| Limitations
The present study limitations were as below: 1.There is a kind of uncertainty about the immunity time frame that has been produced by different types of vaccinations, and longtime studies regarding the Covid-19 vaccination efficacy are insufficient and demanded.It requires more research to support it.
2. Given the new virus variants emerging from the coronavirus such as the Omicron variant, only one of the included studies has been dealt with and its effectiveness has been proven by the authors of the article, but the effectiveness of other current vaccines can be doubted, so more research is needed to measure the cross-protection from current vaccines on new variants of the virus.
3. Due to language limitations, our access is limited only to English studies and we could not use the studies conducted in other languages.

| CONCLUSION
It would presumably be cost-effective if the production of approved vaccines were further developed and applied worldwide.The prioritization of vulnerable target groups, such as high-risk populations or the elderly, into productive populations, has generally posed challenges and critics in professional ethics.We suppose that if primary vaccination at a reasonable cost can reduce the transmission among the population with a higher chance and also prevent the transmission of the disease in the communities rather than just prevention of the disease, especially as a booster dose, its supply with the support of the world community in

1 . 1 . 3 .
Study design: economic assessment reports such as cost analysis, CEA, cost-utility analysis (CUA), and cost-benefit analysis (CBA) 2. Studied cases: vaccinated individuals against Covid-19 3. Intervention: Types of Covid-19 vaccines 4. Comparators: no vaccination 5. Outcome: any outcomes for economic evaluations ICER (incremental cost-effectiveness ratio) as cost per life-year gained (LYG), cost per case averted, cost per quality of adjusted-life years (QALY), cost per Disability-adjusted life years (DALYs), and net marginal benefit of interventions Exclusion criteria The study language other than English 2. The other types of studies such as the short reports, summaries, commentaries, conference abstracts, protocols, cost saving analysis, case reports or case series, editorials, letters and review articles The literature was not available in full text discount rate Direct costs and indirect costs Note: QALY, quality-adjusted life-year; LY: life year; DALYs: disability-adjusted life years; PSA: probability sensitivity analysis, CEA: cost-effectivenenss analysis, CBA: cost-benefit analysis; EFF: effectiveness; HB02: Sinopharm (HB02)-associated vaccine name; BBIBP-CorV: The Sinopharm BIBP COVID-19 vaccine name; BNT162b2: an mRNA-based vaccine developed by Pfizer/BioNTech; rAd26-S + rAd5-s: The Janssen COVID-19 vaccine; ChAdOx1: The ChAdOx1nCoV-19 vaccine (AZD1222) was developed at Oxford University and consists of a replication-deficient chimpanzee adenoviral vector ChAdOx1; Ad26.COV2.S: The Janssen COVID-19 vaccine.ICER: incremental cost-effectiveness ratio; NMB: net monetary benefit, Re: effective reproduction numbers, CN¥: Chinese yuan; NMB, net monetary benefit, BCR1: benefit-cost ratio payer perspective; BCR2: benefit-cost ratio societal perspective; ICUR: indicates incremental cost-utility ratio.T A B L E 2 CHEERS checklist.engagement with patients and others affected by the study 21 presented (1 score), P: partially presented (0.5 score), N: no presented (0 score).

From a payer
perspective, a dollar invested in the vaccine would result in a return of $2.79, $4.77, and $7.21 for Moderna, Pfizer, and AstraZeneca, respectively.Base on a community perspective, one dollar of investiture conducts to throwbacks of $6.05, $10.39, and $14.46 for Moderna, Pfizer, and AstraZeneca, respectively.In addition, the cost-benefit ratio for all three vaccines increases when the value of statistical life and losses to the global economy and education are taken into account.31All three vaccines were dominant against non-vaccination with a coverage rate of 70%.The Moderna vaccine achieved an average of 0.8284 quality-adjusted life days (QALDs) per person at a lower cost, indicating that the Moderna vaccine was a dominant strategy against vaccine absence (ICUR = 321.14).The Pfizer vaccine QALDs were similar to the Moderna vaccine ($31 per dose), but due to the cheaper price of the Pfizer ($14 per dose), more cost savings were observed compared to the Moderna (ICUR = −356.7512).For the AstraZeneca vaccine, the incremental QALDs were smaller than the other two vaccines (0.7456).Although it was cheaper than the other two vaccines (the US $5 per dose), it also had the lowest reduction in incremental costs (ICUR = 341.4381)due to higher demand for medical needs.31The cost per QALY obtained related to the vaccination of the Polish general population was 6249 PLN.In age groups of 60-69 and over 80 years old, vaccination has been assigned as more effective and less expensive compared to no vaccination.And with vaccination in age groups of 40-49 and 30-39, the incremental cost per gained QALY was 28,135 and 67,823 PLN, respectively.Increased risk of hospitalization and hospitalization costs have a greater effect on ICER in the sub-population of the 60-69 years compared to the youth age groups.Under the severe and acute conditions of the disease, except for those over 80, vaccination would not be known cost-effective in all populations (Table many low-and middle-income countries will decline significantly the mortalities and morbidities' rate of Covid-19 disease and hinder the boomerang effect for other countries with adequate measurements for the disease management.Although some studies have shown a significant economic correlation between the value of the vaccine and different age groups, especially in prioritized geriatrics groups, as well as booster vaccination in the context of increasing epidemics with new virus variants; it is suggested that due to the positive externalities of vaccination, primary mass vaccination, with the help of COVAX-19TM, could be considered a reliable way to combat viral epidemics compared to the loss of individual lives and the economic and educational disturbances around the world.AUTHOR CONTRIBUTIONS Dolatshahi Zeinab: Data curation; formal analysis.Nargesi Shahin: Resources; software; supervision; validation; visualization; writingoriginal draft; writing-review & editing.Mezginejad Fateme: Investigation; methodology; project administration.Bagheri faradonbeh Saeed: Conceptualization; data curation.